Focusing on deep sleep-wake brain regions in the context of Alzheimer's disease pathogenesis: a multi-modal, high-resolution neuroimaging approach

The increased prevalence of Alzheimer’s disease (AD) in our ageing society constitutes an urgent, far-reaching public health concern.

In the worldwide effort to identify leverage points to prevent or delay the onset of AD, sleep has recently emerged as a potent modifiable factor to slow down the hallmark pathophysiological processes of the disease, namely amyloid-beta and tau protein accumulation together with neurodegeneration.

Crucially, the brain regions that regulate sleep and wakefulness are the first to be affected by AD pathology in the preclinical stages of the disease, but their role in the link between sleep-wake disruption and AD pathogenesis has so far been critically overlooked, due to the inherent difficulty to image them in vivo in humans.

In this project, I will take an innovative approach, by using state-of-the-art multimodal neuroimaging methods to investigate the contribution of these brain regions to sleep-wake quality in the earliest stages of the disease, and ultimately to AD-related trajectories.

The underlying hypothesis is that worse structural and functional integrity of key sleep-wake nuclei will be associated with poorer sleep-wake phenotypes in the context of AD pathology, and will in turn hasten clinical symptomatology. The unmatched scientific expertise and resources provided by the team of Prof.

Johnson at Massachusetts General Hospital will constitute an outstanding multidisciplinary environment to further develop my knowledge in advanced neuroimaging techniques and statistical modeling approaches, and to bolster my multifaceted international research network.

The wide range of scientific and management skills acquired throughout this fellowship, combined with the international exposure and the resulting close collaborations between European and American research groups, will be key for my future career in Europe as an independent researcher contributing to the global endeavour to improve the earliest detection and prevention of AD.